day 1 - hepatitis, cirrhosis and liver failure Flashcards
(38 cards)
liver macroanatomy
The liver is the largest internal organ in the body, consisting of right and left lobes, and smaller caudate and quadrate lobes. The normal adult liver weighs 1400 to 1600 g. It has a dual blood supply, consisting of the portal vein and the hepatic artery, and is drained by the hepatic vein. From a functional point of view, the liver is divided into sectors and segments, corresponding to the vascular supply and biliary drainage.
what is the port hepatis
The porta hepatis is the region where the hepatic artery and portal vein enter the liver and the common bile duct exits.
liver microanatomy
Hepatocytes are polygonal cells arranged in trabeculae, or liver cell plates, that are 1 – 2 cells thick. They are stable cells, and are able to replicate and regenerate in response to a stimulus, such as resection at surgery. The vascular spaces between the hepatocyte plates are called sinusoids and are lined by sinusoidal endothelial cells, which have fenestrae (windows) facilitating fluid and molecular exchange between the vascular space and the space of Disse (the space between the sinusoids and the hepatocytes, which contains extra-cellular matrix). The blood feeding into the sinusoids comes from both the hepatic artery and the portal vein branches, and the drainage is via the terminal hepatic venules, tributaries of the hepatic vein.
bile drainage path from liver
Bile drainage begins with the bile canaliculi - formed by the contact surfaces of hepatocytes - which drain into thin walled canals (canals of Hering and bile ductules), and then into portal bile ducts. These drain into larger septal ducts, segmental ducts, and main right and left hepatic ducts.
what are the ‘portal tracts’
Portal tracts contain branches of the hepatic artery, portal vein, and bile duct (the portal triad), set in fibro-elastic connective tissue. The meeting of the portal tract with the limiting plate of hepatocytes is called the interface, and is one of the sites of inflammatory activity in hepatitis. Nerves are also present in the portal tract, and are part of the autonomic nervous system.
what are Kupffer cells
macrophages attached to the endoluminal surface of the sinusoidal endothelium, that have a main function of phagocytosis
what do hepatic stellate cells do
hepatic stellate cells (also known as Ito cells, which lie in the space of Disse). In their quiescent state, Ito cells are involved with the storage of vitamin A, but when activated in response to hepatic injury they can transform into myofibroblast-like cells, and begin to lay down collagen
what is a liver lobule (Kiernan)
The lobule is an hexagonal area of liver parenchyma centred on a tributary of the hepatic vein (the central vein), and is surrounded by portal tracts.
what is the liver acinus
the liver acinus, proposed by Rappaport. An acinus is an area of liver parenchyma centred on two portal tracts, which extends to the terminal hepatic venule (the central vein of the hepatic lobule). It can be subdivided into zones1-3, from portal tract to hepatic venule. Zone 3, around the terminal hepatic venule, is the least perfused area and is prone to various types of damage, particularly viral, toxic and ischaemic injury.
the most important clinical manifestations of acute liver damage
Probably the most important clinical manifestations of acute liver damage are tender hepatomegaly, jaundice, and coagulopathy, as well as the less specific malaise and abnormal LFTs. Severe acute liver damage may lead to coma and death.
biliary atresia.
Biliary atresia is a disease of the bile ducts that affects only infants. Bile is a digestive liquid that is made in the liver. It travels through the bile ducts to the small intestine, where it helps digest fats.
In biliary atresia, the bile ducts become inflamed and blocked soon after birth. This causes bile to remain in the liver, where it starts to destroy liver cells rapidly and cause cirrhosis, or scarring of the liver.
primary biliary cirrhosis (PSC)
- Presumed auto-immune aetiology.
- F:M ratio > 6:1.
- Anti-mitochondrial Ab (M2 fraction) highly specific.
- Microscopic features: destruction of intrahepatic bile ducts, lymphocytic infiltrate, granuloma formation, ductular proliferation, and cholestasis.
- Progressive fibrosis.
primary sclerosing cholangitis (PBC).
- ERCP and radiological diagnosis.
- Beading on cholangiography.
- Scarring and destruction of extrahepatic +/- intrahepatic bile ducts.
- Fibrosis of bile ducts, lymphocytic infiltrate, obliteration of lumen.
- Associated with UC.
- Increased risk of cholangiocarcinoma.
first stage of liver pathology
fatty liver - This is a common but non-specific reactive change with many causes (alcohol, diabetes mellitus, obesity, drugs/toxins, starvation, etc) whereby the hepatocytes accumulate lipid droplets in the cytoplasm. The severity varies with the severity of the insult, and it is usually reversible on removal of the stimulus.
Macroscopic changes
The liver is enlarged, soft, yellow and greasy.
Reye’s syndrome
Reye syndrome or Reye’s syndrome is a potentially fatal syndrome that has numerous detrimental effects to many organs, especially the brain and liver, as well as causing a lower than usual level of blood sugar (hypoglycemia).[1] The classic features are a rash, vomiting, and liver damage. The exact cause is unknown and, while it has been associated with aspirin consumption by children with viral illness, it also occurs in the absence of aspirin use.
The disease causes fatty liver with minimal inflammation and cerebral edema (swelling of the brain). The liver may become slightly enlarged and firm, and there is a change in the appearance of the kidneys. Jaundice is not usually present.[3]
Reye syndrome largely affects children. Cases in adults are extremely rare and are more responsive to treatment. Early diagnosis is vital; although most children recover with supportive therapy, it may lead to severe brain injury and death.
Steatohepatitis
A second form of fatty change - microvesicular steatosis - is rare but important, as it
usually indicates a severe metabolic derangement (e.g. acute fatty liver of pregnancy, Reye’s syndrome, mushroom poisoning).
causes of acute hepatitis
This group of disorders is acute in onset, usually over a couple of weeks. A characteristic pattern of damage is seen pathologically. Many things have been found to be responsible for inflammation of the liver.
Aetiology
• Hepatotropic viruses - A to E, with more being described (see Robbins, 6th edition, Table 19-3, p. 856). HCV often has a subclinical or asymptomatic acute phase.
• Drugs/toxins – these can have a predictable, dose dependent toxicity (e.g. paracetamol), or an idiosyncratic, patient-related effect (e.g. antibiotics, such as flucloxacillin). Drugs and toxins can also be responsible for conditions other than acute hepatitis, e.g. cholestasis.
• Alcohol - distinctive microscopic appearances are seen (see above).
• Other infections – systemic viral infections can involve the liver, including infectious
mononucleosis (Epstein Barr virus), cytomegalovirus, rubella, adenovirus, herpes,
enterovirus in the newborn or immunosuppressed, and yellow fever.
• Autoimmune liver disease may also present acutely, although it is - strictly speaking -
considered a chronic liver disease.
what is chronic hepatitis
The strict definition of chronic hepatitis is diffuse inflammation of the liver lasting longer than 6 months, although clinico-pathological evidence of disease may be present within this timeframe, allowing diagnosis. The symptoms, signs, and LFTs may vary both between patients and with time.
Diagnosis depends on a combination of clinical, chemical, pathological and immunological findings.
aetiology of chronic hepatitis
• Hepatotropic viruses: HBV +/- HDV, HCV (HAV and HEV never cause chronic hepatitis). Treatment is with antiviral agents and interferon.
• Auto-immune: predominantly affects females (70%), with high auto-antibody titres (anti-smooth muscle, anti-nuclear, and/or anti-mitochondrial antibodies). Dramatic response to treatment with immunosuppressive medication.
• Rarely caused by drugs or toxins, as liver toxicity is usually identified, and medication ceased or changed.
The progression of chronic hepatitis is related to its aetiology, and some host factors, particularly the integrity of the immune system. For example, HCV infection is much more rapidly progressive post-transplant, or in the setting of HIV co-infection.
what is cirrhosis
A diffuse process characterised by fibrosis and a conversion of normal architecture into structurally abnormal nodules.
Regeneration of nodules may also be present, which gives the nodules a more rounded shape, but it is not necessary to see this to make the diagnosis of cirrhosis. The best classification of cirrhosis is by aetiology, e.g. alcoholic cirrhosis. This may be reflected in the morphology or size of the nodules, which gave rise to the description of macro- and micro-nodular cirrhosis, but this is an unreliable method for determining the aetiology, particularly in the setting of more than one aetiological factor. Traditionally, liver fibrosis and cirrhosis was thought to be a progressive and irreversible, but recent papers have suggested that this may not always be the case, and improved treatment regimes are being investigated.
common causes of liver cirrhosis
- Chronic viral hepatitis.
- Alcoholic liver disease.
- Auto-immune liver disease.
- Metabolic liver diseases.
- Biliary diseases.
- Vascular (rare) – e.g. chronic Budd–Chiari syndrome.
- Not strictly a cause, but those of undetermined cause may be labelled ‘cryptogenic’ – current opinion is that some of these may be due to NASH.
complications with liver cirrhosis
Cirrhosis can be described clinically as being compensated or decompensated, relating to the effect on the person’s wellbeing. The main complications are related to the following:
• Hepatocellular failure is most evident in decompensated cirrhosis, with jaundice,
hypoalbuminaemia, and coagulopathy. Lesser degrees of these may be seen in compensated cirrhosis.
• Portal hypertension (which may have causes other than cirrhosis, such as
schistosomiasis) – this leads to the development of porto-systemic anastomoses. Common sites for the formation of these anastomoses are in the oesophagus, around the spleen, around the umbilicus (caput medusae), and in the perianal veins. Varices often form at these sites of anastomosis, which are at risk of rupture and life- threatening haemorrhage.
- Ascites is formed, influenced by the combination of portal hypertension and hypoalbuminaemia.
- Porto-systemic shunting of blood is possible through these anastomoses, bypassing the liver and first pass metabolism of drugs and toxins.
- Encephalopathy ensues as toxins, particularly ammonia, reach the central nervous system.
- Systemic infections with enteric organisms are more common, particularly in relation to ascites and spontaneous bacterial peritonitis.
- Hepatocellular carcinoma is increased in all causes of cirrhosis, but there are some with a higher incidence, e.g. HCV, HBV, haemochromatosis.
what is hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the most common primary malignant liver neoplasm, and has aetiological associations with HBV, HCV, aflatoxins, chemicals, and metabolic liver diseases. Epidemiologically, there is worldwide geographical variation in the pattern of presentation of HCC, largely related to the endemicity of HBV infection, and other factors such as aflatoxin exposure.
primary malignancies of the liver
- Hepatocellular carcinoma (HCC)
• Cholangiocarcinoma – associated with UC, PSC, liver flukes.
• Angiosarcoma –rare and associated with exposure to vinyl chloride or arsenic.
• Hepatoblastoma – a rare neoplasm of young childhood.
• Lymphoma and sarcoma can also affect the liver.